title: Artemisinin-induced parasite dormancy: a plausible mechanism for treatment failure.
abstract: BACKGROUND
  Artemisinin-combination therapy is a highly effective treatment for uncomplicated falciparum malaria but parasite recrudescence has been commonly reported following artemisinin (ART) monotherapy. The dormancy recovery hypothesis has been proposed to explain this phenomenon, which is different from the slower parasite clearance times reported as the first evidence of the development of ART resistance.
  
  
  METHODS
  In this study, an existing P. falciparum infection model is modified to incorporate the hypothesis of dormancy. Published in vitro data describing the characteristics of dormant parasites is used to explore whether dormancy alone could be responsible for the high recrudescence rates observed in field studies using monotherapy. Several treatment regimens and dormancy rates were simulated to investigate the rate of clinical and parasitological failure following treatment.
  
  
  RESULTS
  The model output indicates that following a single treatment with ART parasitological and clinical failures occur in up to 77% and 67% of simulations, respectively. These rates rapidly decline with repeated treatment and are sensitive to the assumed dormancy rate. The simulated parasitological and clinical treatment failure rates after 3 and 7 days of treatment are comparable to those reported from several field trials.
  
  
  CONCLUSIONS
  Although further studies are required to confirm dormancy in vivo, this theoretical study adds support for the hypothesis, highlighting the potential role of this parasite sub-population in treatment failure following monotherapy and reinforcing the importance of using ART in combination with other anti-malarials.
authors.affiliation: Malaria Drug Resistance and Chemotherapy Laboratory, Queensland Institute of Medical Research, Brisbane, Australia.
authors.forename: Andrea
authors.initials: A
authors.lastname: Codd
authors.forename: Franka
authors.initials: F
authors.lastname: Teuscher
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Kyle
authors.forename: Qin
authors.initials: Q
authors.lastname: Cheng
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Gatton
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D016778:Malaria, Falciparum / Q000188:drug therapy*; D015233:Models, Statistical; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D017211:Treatment Failure
chemical_list: D000962:Antimalarials; D037621:Artemisinins; C031327:artemisinin